Physical capture and release of drug molecules, water and cations by a smectite clay

Abstract

As a result of their unique properties, such as porosity, water adsorption ability, charged nano-layered structure and swelling capacity, clay minerals have been widely used through human history. The main focus of this PhD project was to extend these applications and explore the potential of using the synthetic smectite Li-Fluorohectorite (Li-Fh) as a carrier for the antibacterial agent Ciprofloxacin (CIPRO, C17H18FN3O3), as represented in figure 1.

Figure 1: Sketch showing the intercalation of CIPRO in the interlayer spaces of Fluorohectorite via cation exchange.

Based on experimental investigations, using UV-Vis spectroscopy, X-rays powder diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDS), Thermogravimetric Analysis coupled to Infrared Spectroscopy (TGA/IR) and Inelastic Neutron Scattering (INS), we demonstrated that at acidic conditions Li-Fh can capture at least 25 % more CIPRO than any other system reported on literature. Additionally, results obtained for drug capture as a function of pH indicates that CIPRO replaces the interlayer cations, Li in this case, assuming its function and compensating the electric charge of the clay layers. Interestingly, the drug presence into the interlayer space of Li-Fh facilitates the water removal from the clay’s interlayer space. Furthermore, release studies of CIPRO from Li-Fh in conditions mimicking synthetic gastric acidic juice showed that the drug’s release is thermally activated and diffusion-controlled. Of more interest are the results from toxicological and effectiveness tests, demonstrating that Fh does not interfere with the drug’s action and does not cause adverse effects on human cells.

In order to complement and support our findings, cation exchange process in LiFh and the hydration pathways in NiFh (Fh having nickel as charge compensating cation) were also analyzed by means of XRD and EDS. It was found that, the exchange from Li+ to Na+ and to Ni2+ occurs very fast, while the reverse is a much slower process. This result corroborates with the selectivity rule among cations, which states that larger cations have preference over smaller ones. Indeed, this same behavior was observed during the capture and release of CIPRO, where capture was much faster than release.

To conclude, the ensemble of the results obtained during the development of this PhD thesis adds Fh to the list of promising drug delivery systems. Our findings can be easily extended to other clay minerals and drug molecules, as the results and experimental conditions summarized in this work can serve as foundation for setting up novel studies.